Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed with Lecigon. The following interactions are known from combinations of levodopa/carbidopa and entacapone/levodopa/carbidopa.

Caution is needed in concomitant administration of Lecigon with the following medicinal products: 
Antihypertensives
Symptomatic postural hypotension has occurred when combinations of levodopa and a decarboxylase inhibitor are added to the treatment of patients already receiving antihypertensives. Dose adjustment of the antihypertensive agent may be required.

Antidepressants
Administration of non-selective MAO inhibitors and selective MAO type A inhibitors are contraindicated for use with Lecigon. Treatment with these inhibitors must be discontinued at least two weeks prior to initiating therapy with Lecigon (see section 4.3).

There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant administration of tricyclic antidepressants and carbidopa/levodopa preparations.

A significant number of patients with Parkinson's disease have been treated with the combination of levodopa, carbidopa, entacapone and tricyclic antidepressants and no pharmacodynamic interactions have been observed. However, caution should be exercised when using antidepressants at the same time as Lecigon.
Anticholinergics
Anticholinergics may act synergistically with levodopa to reduce tremors. However, combined use may exacerbate abnormal involuntary movements. Anticholinergics may decrease the effects of levodopa by delaying its absorption. An adjustment of the dose of Lecigon may be required.

Other anti-Parkinsonian medicinal products
Lecigon can be taken concomitantly with the recommended dose of an MAO inhibitor with selectivity for MAO type B, e.g. selegiline hydrochloride. Concomitant use of selegiline and levodopa/carbidopa has been associated with serious orthostatic hypotension. A reduction of the dose of Lecigon may therefore be required when adding selective MAO-B inhibitor.

Amantadine and dopamine agonists like piribedil have a synergistic effect with levodopa and may increase levodopa-related adverse events. An adjustment of the dose of Lecigon may be required.

Other medicinal products
Dopamine receptor antagonists (some antipsychotics, e.g. phenothiazines, butyrophenons and risperidone, and antiemetics, e.g. metoclopramide), benzodiazepines, isoniazide, phenytoin and papaverine can reduce the therapeutic effect of levodopa. Patients taking these medicinal products together with Lecigon should be observed carefully for loss of therapeutic response.

Sympathicomimetics may increase cardiovascular adverse events related to levodopa.

Levodopa forms a chelate with iron in the gastrointestinal tract, leading to reduced absorption of levodopa. Lecigon and oral iron preparations should therefore be taken at least 2–3 hours apart. For example, the iron preparation can be taken before bedtime if the patient does not use the pump during the night.

Due to entacapone's affinity for P450 2C9 in vitro (see section 5.2), Lecigon may affect medicinal products whose metabolism is dependent on this isoenzyme, such as S-warfarin. However, in an interaction study with healthy volunteers, entacapone did not change plasma levels of S-warfarin, while the area under the curve (AUC) for R-warfarin increased on average by 18% (90% confidence interval: 11–26%). The INR values increased on average by 13% (90% confidence interval: 6–19 %).
A control of INR is therefore recommended when treatment with Lecigon is initiated for patients receiving warfarin.

The effect of administration of antacids and Lecigon on the bioavailability of levodopa has not been studied.

Food interactions
As levodopa is competitive with certain amino acids, the absorption of levodopa may be disturbed in patients who are on a protein-rich diet.